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Biomarker-based bleeding scores deliver superior predictive accuracy over conventional clinical risk models in atrial fibrillation.
Atrial fibrillation (AF) substantially amplifies the risk of ischemic stroke and systemic thromboembolism, making oral anticoagulation (OAC) a cornerstone of management. While OAC potently minimizes stroke risk, it also raises the likelihood of bleeding, and existing clinical bleeding risk scores show only modest predictive accuracy. Overlapping risk factors for stroke and bleeding further complicate treatment decisions.
A new narrative review evaluated whether circulating biomarkers can improve bleeding risk prediction in AF patients receiving OAC and how these markers can be integrated into personalised risk-assessment strategies. The review published in "Cardiovascular Diagnosis and Therapy" analyzed evidence from major randomized trials and large cohort studies assessing bleeding-related biomarkers in anticoagulated AF patients. Key biomarkers evaluated included cystatin C, D-dimer, growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin (hs-cTn), interleukin-6 (IL-6), N-terminal prohormone brain natriuretic peptide (NT-pro-BNP), and von Willebrand factor (vWF).
Their prognostic performance, contribution to biomarker-based risk scores—such as the ABC (Age, Biomarkers, Clinical history)-bleeding score—and their ability to boost predictive accuracy beyond traditional clinical tools were examined. Across studies, GDF-15 consistently emerged as a strong, independent forecaster of major bleeding and mortality. Its prognostic value has been validated in large AF trials, including Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), Edoxaban Versus Warfarin in Patients with Atrial Fibrillation trial (ENGAGE AF-TIMI 48), and Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE).
Elevated hs-cTn and D-dimer levels were also independently linked to higher bleeding chances and are key components of the ABC-bleeding score, which has illustrated better predictive performance than conventional scores like HAS-BLED. Additional biomarkers—cystatin C as an indicator of renal dysfunction, along with vWF and IL-6—were related to adverse outcomes, although their predictive strength varied across studies. Overall, incorporating circulating biomarkers into bleeding risk scores enabled more accurate and individualized risk stratification in AF. This may help clinicians and patients better balance bleeding and stroke risks, enabling more individualised treatment decisions and potentially curtailing the overall burden of both complications.
Cardiovascular Diagnosis and Therapy
Biomarkers of increased bleeding risk in patients with atrial fibrillation on oral anticoagulation: a narrative review
Abdalazeem Ibrahem et al.
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